DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The present application was filed on 09/12/2022. This application is a 371 of PCT/IB2021/000140 filed on 03/12/2021 which claims benefit of U.S. Provisional Patent Application 62/989,571 filed on 03/13/2020 and claims benefit of 63/086,536 filed on 10/01/2020.
Claim status
Claims 1-92 are canceled. Claims 93-112 are pending and examined herein.
Specification
The disclosure is objected to because of the following informalities: in par.105, the term “secribe” is likely a misspelling of --describe--.
Appropriate correction is required.
Claim Objections
Claim 93 is objected to because of the following informalities: step (d) recites “detecting one or both of the released detection reagent or capture reagent”, which should be “detecting one or both of the released detection reagent and capture reagent”.
Claim 94 is objected to because of the following informalities: line 2 missing --a-- in front of “second anchor element”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 93-112 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 93 recites “A method of detecting and/or quantifying an analyte in a sample, the method comprising:(a) contacting the sample with a complex comprising: (i) a support, (ii) a capture reagent releasably coupled to the support, (iii) a detection reagent releasably coupled to the support, wherein the capture reagent and detection reagents are configured to simultaneously bind to the analyte; (b) decoupling the detection reagent from the support; (c) decoupling the capture reagent from the support; and (d) detecting one or both of the released detection reagent or capture reagent.”
The claim does not recite how the analyte in a sample is detected or quantified. Instead, the claim recites detecting the released detection reagent or capture reagent, or both of the released detection reagent and capture reagent. It is not clear that how the detection of one or both of the released detection reagent and capture reagent relates to the detection of the analyte.
Though the detection reagent and capture reagent are configured to simultaneously bind to the antigen, it does not mean the complex of capture reagent – target analyte – detection reagent is always formed in the assay. Thus, the released detection reagent or capture reagent at step (d) can be in the complex of capture reagent – target analyte – detection reagent or in the free-form without binding to the target analyte. The claim is indefinite for failing to particularly point out how to detect the analyte via detecting the released detection reagent and/or capture reagent, for example, when the released detection reagent and/or capture reagent are in the complex with the analyte and when the released detection reagent and/or capture reagent are not in the complex with the analyte.
In one embodiment, the detection reagent can comprise a label, which the labeled detection reagent can be detected after the detection reagent is released from the support (see specification par.52) even if the detection reagent does not bind to the target analyte. If detecting the released detection reagent or capture reagent in the complex of capture reagent – target analyte – detection reagent, the amount of the released detection reagent or capture reagent in a complex can be positively correlated with the amount of the analyte (see specification par.62). However, if detecting the released detection reagent or capture reagent in free-form, the amount of the released detection reagent or capture reagent in a complex can be inversely correlated with the amount of the analyte.
Therefore, the claim is indefinite for failing to particularly point out how to detect the analyte by detecting one or both of the released detection reagent and capture reagent.
Claims 94-112 are rejected because they depend on the rejected claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 93-101 and 112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer (US20200191779) in view of Smith (US20160153973).
For claim 93, Glezer teaches method for measuring the amount of analyte bound to a solid phase (see par.11) comprising: contacting the sample with a complex comprising: a support and a capture reagent releasably coupled to the support and decoupling the capture reagent from the support (see par.6: teaching that contacting a sample comprising a target analyte with a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent; see par.23: teaching that releasing said complex by cleaving said first binding reagent from said particle).
Glezer also teaches the capture reagent and detection reagents are configured to simultaneously bind to the analyte (see at least par.24: teaching that contacting said complex with a second binding reagent, wherein said second binding reagent binds to said complex);
decoupling the capture reagent from the support (see par.6: teaching that contacting a sample comprising a target analyte with a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent; see par.23: teaching that releasing said complex by cleaving said first binding reagent from said particle), although Glezer does not teach that the detection reagent is released from the support, the complex of a first binding reagent, an analyte, a second binding reagent and detectable label is cleaved off from the support after the capture reagent is released from the support because the detection reagent of Glezer is not originally bound on any support; and
detecting one or both of the released detection reagent and capture reagent (see par(s).24-26: teaching that the complex of a first binding reagent, an analyte, a second binding reagent and detectable label is measured).
Glezer does not teach a detection reagent releasably coupled to the support and decoupling the detection reagent from the support.
Smith teaches a method of detecting and/or quantifying an analyte in a sample (see Abstract: disclosing a method and system which uses cleavable linkers to detect an analyte in an immunoassay), the method comprising:
(a) contacting the sample with a complex comprising (see par.40: teaching that contact of the sample with the active surface):
a support (see par.26: a solid support 110),
a capture reagent coupled to the support (see par(s).26-27 and Fig.1: a capture antibody coupled to the support via a linker 120),
a detection reagent releasably coupled to the support (see par(s).26-27 and Fig.1: a detection antibody coupled to the support via a cleavable linker 130),
wherein the capture reagent and detection reagents are configured to simultaneously bind to the analyte (see at least par.28 or par.42: teaching that the analyte is an antigen with epitopes that bind to a paratope on both the capture antibody 140 and the detection antibody 150; when the analyte reacts with both paratopes, a complex is formed; the capture antibody and the detection antibody both bind to the analyte when it is added to the plate);
(b) decoupling the detection reagent from the support (see par.28, par.41 and Figs.1-2: teaching that when the analyte reacts with both paratopes, a complex is formed and the cleavable linker is cleaved);
(d) detecting one or both of the released detection reagent and capture reagent (see par.26: teaching that the detection antibody is bound to the detection agent; see in par.29: teaching that the detection agent reacts with a substrate to form a new molecule that absorbs light, so that the color and intensity of light in the sample is measured to determine the amount of analyte in the sample).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Glezer, using a detection reagent releasably coupled to the support, then released from the support in a method of detecting an analyte in a sample as taught by Smith. A person of ordinary skill in the art would have been motivated to immobilize a detection reagent on a support via a cleavable linker because Smith teaches that the use of cleavable linker on detection reagent allows for a reduction in wash steps, incubation time, and potential for user error in a method of detecting and quantifying analyte. It also allows for intramolecular binding kinetics for quickly binding an analyte to two antibodies. See Smith in Abstract.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Glezer and Smith because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent. Either detection reagent is soluble in a solution as in Glezer or is immobilized on the support as in Smith, the complex of capture reagent - analyte - detection reagent is still formed, so the analyte can be detected.
For claims 94-97, Glezer and Smith teach the method of claim 93, wherein the support further comprises a first anchor element as in claims 94 and 97, wherein the capture reagent comprises a first hook element coupled thereto, and wherein the first hook element is coupled to the first anchor element as in claim 95 (see Glezer in par.157 teaches a method of coupling a capture reagent on a solid support by using oligonucleotides and their complementary strands: “Magnetic particles are coated with oligonucleotides … Conjugates are formed comprising antibodies against analytes of interest and oligonucleotides complementary to the oligonucleotides on the particles”). Since Glezer uses the detection reagent in a soluble form, Glezer does not teach the method of linking and cleaving the detection reagent on the support as in claims 94, and 96-97.
For claim 94, Smith teaches a second anchor element coupled thereto (see Smith par.26 and Fig.1: teaching that both capture and detection antibodies are linked to the support via linkers 120 and 130), and the detection reagent is releasably coupled to the support via the second anchor element (see Smith in par(s).26-27: teaching that the linkers are linked to the support and the cleavable linker 130 is linked to the detection reagent).
For claim 95, Smith teaches wherein the capture reagent comprises a first hook element coupled thereto, and wherein the first hook element is coupled to the first anchor element (see Smith in par.25 and Fig.13: teaching that the capture reagent is conjugated with an oligonucleotide, the oligonucleotide then reacts with the complimentary linker on the solid support which is a plate).
For claim 96, Smith teaches wherein the detection reagent comprises a second hook element coupled thereto, and wherein the second hook element is releasably coupled to the second anchor element (see Smith in par.25 and Fig.13: teaching that the detection reagent is conjugated with an oligonucleotide, the oligonucleotide then reacts with the complementary linker on the solid support which is a plate, see Smith in par(s).26-28: teaching that the detection reagent can be released from the support by the cleavable linker).
Both Glezer and Smith teach a method of linking a reagent on a support by using an oligonucleotide on the support and its complementary oligonucleotide conjugated with the reagent (e.g., capture or detector reagent), wherein the linking is releasable (see Glezer in par(s).158-161 or see Smith in par.28).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of linking a reagent on a support taught by Glezer and Smith, coupling a releasably detection reagent on the support in a method of detecting an analyte in a sample taught by Glezer in view of Smith because Glezer and Smith teaches this method can be used for linking a reagent on a support and for releasing the reagent as desired. A person of ordinary skill in the art would have been motivated to immobilize a releasable detection reagent on a support because Smith teaches that the use of cleavable linker on detection reagent allows for a reduction in wash steps, incubation time, and potential for user error in a method of detecting and quantifying analyte. It also allows for intramolecular binding kinetics for quickly binding an analyte to two antibodies. See Smith in Abstract.
Since Glezer and Smith support for the method of linking and cleaving a reagent on the support by using an oligonucleotide on the support and its complementary oligonucleotide conjugated with the reagent, e.g., the capture reagent or the detector reagent in respectively, one having an ordinary skill in the art would have had a reasonable expectation of success in applying the method taught by Glezer and Smith to couple the releasable detection reagent on the support so that the releasable detection reagent can be used in the method of Glezer in view of Smith.
For claims 98-99, Glezer and Smith teach the method of claim 93, wherein the support further comprises an anchor element coupled thereto, wherein the capture reagent is releasable coupled to the support via the anchor element, and the capture reagent comprises a first hook element coupled thereto (see Glezer in par.157 teaches a method of coupling a capture reagent on a solid support by using oligonucleotides and their complementary strands: “Magnetic particles are coated with oligonucleotides … Conjugates are formed comprising antibodies against analytes of interest and oligonucleotides complementary to the oligonucleotides on the particles”). Glezer does not teach the capture and detection reagents are releasably linked on the support via the same anchor element on the support as in claims 98-99.
Smith teaches wherein the support further comprises an anchor element coupled thereto (see Smith par.16 and Fig.4), and wherein the capture reagent is releasable coupled to the support via the anchor element and the detection reagent is releasably coupled to the support via the anchor element (see Smith par.16 and Fig.4).
For claim 99, Smith teaches wherein (1) the capture reagent comprises a first hook element coupled thereto (see Smith in par.25 and Fig.13: teaching that the capture reagent is conjugated with an oligonucleotide, the oligonucleotide then reacts with the complimentary linker on the solid support which is a plate), and (2) the detection reagent comprises a second hook element coupled thereto, and wherein the second hook element is releasably coupled to the anchor element (see Smith in par.25 and Fig.13: teaching that the detection reagent is conjugated with an oligonucleotide, the oligonucleotide then reacts with the complementary linker on the solid support which is a plate, see Smith in par(s).26-28: teaching that the detection reagent can be released from the support by the cleavable linker).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of linking a reagent on a support taught by Glezer or Smith, coupling a releasably the detection reagent on the support in a method of detecting an analyte in a sample taught by Glezer in view of Smith because Glezer or Smith teaches this method can be used for linking a reagent on a support and for releasing the reagent as desired. A person of ordinary skill in the art would have been motivated to immobilize a detection reagent on a support via a cleavable linker because Smith teaches that the use of cleavable linker on detection reagent allows for a reduction in wash steps, incubation time, and potential for user error in a method of detecting and quantifying analyte. It also allows for intramolecular binding kinetics for quickly binding an analyte to two antibodies. See Smith in Abstract.
One having an ordinary skill in the art would have had a reasonable expectation of success in combine Glezer and Smith because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent.
Since Glezer and Smith support for the method of linking and cleaving a reagent on the support by using an oligonucleotide on the support and its complementary oligonucleotide conjugated with the reagent, e.g., the capture reagent or the detector reagent in respectively (see Glezer in par(s).158-161 or Smith in par.28 or par.86), one having an ordinary skill in the art would have had a reasonable expectation of success in applying the method taught by Glezer and Smith to couple the releasable detection reagent on the support so that the releasable detection reagent can be used in the method of Glezer in view of Smith.
For claims 100-101, Glezer and Smith teach the method of claim 93, wherein decoupling comprises applying a stimulus that decouples the detection reagent or the capture reagent from the support, wherein the stimulus is a thermal stimulus, photo-stimulus, chemical stimulus, a mechanical stimulus, a radiation stimulus, a biological stimulus, or any combination thereof as in claim 100, wherein decoupling comprises providing a displacer agent as in claim 101 (see Glezer par.93 and par.126: teaching that cleaving step optionally comprises subjecting the complex to increased or decreased temperature, pH changes, competition, or introducing competing ligands (i.e., a displacer); see Smith par.28: teaching that adding a buffer to the solution which decreases the melting temperature of double stranded DNA interactions with the detection antibody linker, see Smith par.86: teaching that the displacer agent is endonucleases, or enzymes that cleave DNA phosphodiester bonds at specific sites within the DNA, or DTT, or singlet oxygen species generated with light in the presence of a singlet oxygen photosensitizer).
For claim 112, Glezer and Smith teach the method of claim 93. Glezer teaches wherein subsequent to (d), the method comprises capturing the detection reagent and/or the capture reagent on a second support.
Glezer teaches that a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent (see par.13); releasing said complex by cleaving said first binding reagent from said particle (see par.16), contacting said complex with a second binding reagent bound to a second solid phase, wherein said second binding reagent binds to said complex (see par.17), measuring the amount of said analyte bound to said second solid phase (see par.18).
The teaching of Glezer supports that the complex of capture reagent – analyte – detection reagent can be captured on a second solid support. By doing this, the analyte in the sample can be concentrated or purified so that it can improve the sensitivity of a subsequent measurement step or it can provide a uniform matrix for subsequent assay steps (see par.128).
Claim(s) 102-104 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer (US20 200191779) in view of Smith (US 20160153973), as applied in claim 93, and further in view of Sano et al. (Immuno-PCR: Very Sensitive Antigen Detection by Means of Specific Antibody-DNA Conjugates, Science vol.258, 120-122, 1992).
For claims 102-104, Glezer and Smith teach the method of claim 93. Glezer teaches measuring the amount of an analyte through the detection of labels which may be attached directly or indirectly to an analyte (see par.131).
They do not teach wherein (d), detecting comprises identifying a nucleic acid molecule corresponding to the detection reagent or capture reagent as in claim 102, wherein identifying the nucleic acid molecule comprises performing a sequencing reaction, a PCR as in claim 103.
They do not teach the method of claim 102, wherein the nucleic acid molecule comprises a barcode sequence, unique molecular identifier sequence, a primer binding sequence, or a combination thereof as in claim 104.
Sano teaches that immuno-polymerase chain reaction (immuno-PCR), was developed in which a specific DNA molecule is used as the marker for an antigen detection system (see Abstract). Given the enormous amplification capability and specificity of PCR, this immuno-PCR technology has a sensitivity greater than any existing antigen detection system, e.g., ELISA (see Abstract).
Sano teaches detecting comprises identifying a nucleic acid molecule corresponding to the detection reagent or capture reagent (see page 120 col.2 par(s).1-2: teaching that an antigen detection system, termed immuno-PCR, in which a specific antibody-DNA conjugate is used to detect antigens, a DNA molecule (marker) is specifically attached to an antigen-antibody complex, and the attached marker DNA can be amplified by PCR)
Sano teaches the nucleic acid molecule comprises a primer binding sequence (see page 120 col.2 par.2: teaching that the attached marker DNA can be amplified by PCR with the appropriate primers, which means the DNA marker comprises a primer binding sequence).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Glezer, detecting an analyte in a sample by identifying a nucleic acid molecule corresponding to the detection reagent or capture reagent as taught by Sano because Sano teaches immuno-PCR technology has a sensitivity greater than conventional antigen detection system, e.g., ELISA as in Glezer (see Glezer par.131). A person of ordinary skill in the art would have been motivated to modify the method of Glezer to improve the sensitivity of the antigen detection assay.
One having an ordinary skill in the art would have had a reasonable expectation of success of combining Glezer and Sano because Glezer measures analytes through the detection of labels which may be attached directly or indirectly to an analyte, and Sano measures analytes through the detection of DNA molecule labels attached to an antigen-antibody complex, thus it would yield a predictable result to one of ordinary skill in the art.
Claim(s) 105-111 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer (US20 200191779) in view of Smith (US 20160153973), as applied in claim 93 above, and further in view of Juncker (WO2019191838).
For claims 105-107, Glezer and Smith teach the method of claim 93. They do not teach the limitations recited in claims 105-107.
Juncker teaches a method of detecting and/or quantifying an analyte in a sample (see in par.78-79: disclosing a method for detecting an analyte from a sample), the method comprising:
(a) contacting the sample with a complex (see in par.78-79: teaching that incubating the sample with the support allowing binding of the capture reagent and the detection reagent to different epitopes on the analyte) comprising: a support (see in par.78-79), a capture reagent coupled to the support (see in par.79: teaching that a capture reagent coupled to the support via a capture strand and an anchor strand), a detection reagent releasably coupled to the support (see in par.79: teaching that a detection reagent coupled to the support via a hook strand and an anchor strand, see par.16: teaching that a detection reagent releasably attached to the anchor strand);
wherein the capture reagent and detection reagents are configured to simultaneously bind to the analyte (see in par.16: teaching that the capture reagent and the detection reagent can simultaneously bind to the analyte);
(b) decoupling the detection reagent from the support (see in par.78: teaching that breaking the bond between the hook strand and the anchor strand by separating the detection reagent and the hook strand from the support);
(d) detecting one or both of the released detection reagent or capture reagent (see in par.16: teaching that the presence of the analyte in the sample is thus determined through detection of the first label on the support after the detection reagent has been released from the anchor strand, since the detection reagent will only remain attached to the support if bound to the analyte in a tertiary complex with the capture reagent).
For claim 105, Juncker also teaches wherein (b), decoupling comprises providing a detectable displacer agent that decouples the detection reagent from the support (see Juncker par.34: teaching that a displacer agent may be any agent capable of specifically breaking or releasing the link between the hook strand and the anchor strand, which detaches the detection reagent from the support; see Juncker par.182: teaching that the label is on a displacer agent hybridizing to the hook strand which is linked to the detection reagent).
For claim 106, Juncker teaches the method of claim 105, wherein the detectable displacer agent is an oligonucleotide (see Juncker par.87 and par.183: displacer agents include but are not limited to a displacement DNA oligonucleotide).
For claim 107, Juncker teaches the method of claim 106, wherein the oligonucleotide comprises a barcode sequence, unique molecular identifier sequence, a primer binding sequence, or a combination thereof (see Juncker par(s).87 and 182-183: teaching that the displacer agent comprises an DNA oligonucleotide and a label; see Juncker par.69,: teaching that a unique DNA sequence can be used as a label, thus the displacement DNA oligonucleotide would comprise an oligonucleotide with a unique sequence).
For claim 111, Juncker teaches the method of claim 105, wherein (d), detecting comprises detecting the displacer agent (see Juncker par.81: teaching that quantifying an amount of the bound analyte by analyzing the displacer agent label remaining on the support, wherein the displacer agent label concentration remaining on the support is in proportion the concentration of the analyte bound).
The method of Juncker provides multiplex sandwich immunoassays with minimal cross-reactivity between reagents that are rapid, sensitive, cost-effective and/or scalable, allowing simultaneous detection and/or quantification of multiple analytes in a sample (see par.14).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Glezer, providing a detectable displacer agent that decouples the detection reagent from the support, wherein the detectable displacer agent is an oligonucleotide comprising a unique molecular identifier sequence, so that an analyte in a sample can be detected by identifying a labeled displacer agent as taught by Juncker. A person of ordinary skill in the art would have been motivated to modify the method of Glezer in view of Smith to improve the sensitivity of the antigen detection assay because the method of Juncker is rapid, sensitive, cost-effective and/or scalable, and allows simultaneous detection and/or quantification of multiple analytes in a sample.
One having an ordinary skill in the art would have had a reasonable expectation of success of combining Glezer and Juncker because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent. Glezer measures analytes through the detection of labels which may be attached directly or indirectly to an analyte, and Juncker also measures analytes through the detection of the detectable displacer agent linked to the detection antibody, so the combination still results in a predictable outcome.
For claims 108-110, Glezer and Smith teach the method of claim 93. While Glezer teaches decoupling the capture reagent from the support by a displacer agent (see Glezer par.93 and par.126: teaching that cleaving step optionally comprises subjecting the complex to increased or decreased temperature, pH changes, competition, or introducing competing ligands (i.e., a displacer), Glezer does not teach wherein (c), decoupling comprises providing a detectable displacer agent that decouples the capture reagent from the support, wherein the detectable displacer agent is an oligonucleotide, and wherein the oligonucleotide comprises a barcode sequence, unique molecular identifier sequence, a primer binding sequence, or a combination thereof.
However, Glezer teaches that the capture reagent is linked to the support via a DNA oligonucleotide linker (see par.157). This method of coupling an agent to a support is similar to the method of coupling the detection reagent on the support taught by Juncker (see Juncker par.63: teaching that the detection reagents are linked to the support via a DNA oligonucleotide linker). Junker also teaches the method of decoupling comprises providing a detectable displacer agent that decouples the detection reagent from the support (see Juncker par.34 and par.182), wherein the detectable displacer agent is an oligonucleotide (see Juncker par.87 and par.183), and wherein the oligonucleotide comprises a barcode sequence, unique molecular identifier sequence, a primer binding sequence, or a combination thereof (see Juncker par(s).87 and 182-183). See the discussion of Juncker in claims 105-106 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Glezer, providing a detectable displacer agent that decouples the capture reagent from the support, wherein the detectable displacer agent is an oligonucleotide comprising a unique molecular identifier sequence, so that an analyte in a sample can be detected by identifying a labeled displacer agent as taught by Juncker. Though Juncker teaches the method of using a detectable displacer agent on the detection agent, it would have been obvious to utilize this known decoupling method taught by Juncker for the purpose of decoupling the capture reagent, and the result would have been predictable because the techniques to couple the capture reagent and the detection reagent are similar, e.g., via a DNA oligonucleotide linker.
A person of ordinary skill in the art would have been motivated to modify the method of Glezer in view of Smith to improve the sensitivity of the antigen detection assay because the method of Juncker is rapid, sensitive, cost-effective and/or scalable, and allows simultaneous detection and/or quantification of multiple analytes in a sample.
One having an ordinary skill in the art would have had a reasonable expectation of success of combining Glezer and Juncker because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent. Glezer measures analytes through the detection of labels which may be attached directly or indirectly to an analyte, and Juncker also measures analytes through the detection of the detectable displacer agent linked to the detection antibody, so the combination still results in a predictable outcome.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 93-94, 100-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-21, 27 and 38-40 of copending Application No. 17/200,680 (‘680). Although the claims at issue are not identical, they are not patentably distinct from each other because:
For claims 93-94, claim 1 of ‘680 encompasses the limitations of the claims.
For claim 100, claims 20-21 and 27 of ‘680 encompasses the limitations of the claim.
For claims 101-107 and 111, claims 1 and 38-40 of ‘680 encompasses the limitations of the claims.
For claims 108-110, claims 1 and 38-40 of ‘680 teaches decoupling the detection antibody by using a detectable displacer agent comprising an oligonucleotide that comprises a primer binding sequence. ‘680 does not teach these limitation on releasing the capture antibody.
However, ‘680 teaches that a capture antibody is coupled to a support via a releasable linker. The teaching is generic to any type of releasable linker. Therefore, it is obvious to apply the releasing method taught for detection antibody on releasing the capture antibody because ‘680 supports for the successfulness of the releasing an antibody from the support.
Claims 95-99 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-21, 27 and 38-40 of copending Application No. 17/200,680 (‘680) in view of Smith (US20160153973). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Application ‘680 teaches the method of claim 93 as discussed above but does not teach the limitations of claims 95-99.
Smith teaches: the capture reagent comprises a first hook element coupled thereto, and wherein the first hook element is coupled to the first anchor element as in claims 95 and 97-99; the detection reagent comprises a second hook element coupled thereto, and wherein the second hook element is releasably coupled to the second anchor element as in claims 96 and 97-99; the support further comprises an anchor element coupled thereto, and wherein the capture reagent is releasably coupled to the support via the anchor element and the detection reagent is releasably coupled to the support via the anchor element as in claim 98.
See discussion of Smith in claim 93 above. The teachings are found in par.16, par(s).25-28 and Fig(s).13-14).
While Smith does not teach the capture reagent coupled on the solid support is releasable, the method of coupling the capture reagent on the solid support taught by Smith is similar to the method of coupling the detection reagent on the solid support taught by Smith. Since the detection reagent of Smith is able to be released from the support, one having an ordinary skill in the art would have had a reasonable expectation of success that the capture reagent of Smith can also be released form the support by using the method of releasing the reagent from a support taught by Smith (see par.28).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of ‘680, coupling the capture antibody and the detection antibody on the support via a releasable linker as taught by Smith. One having an ordinary skill in the art would have had a reasonable expectation of success of combining ‘680 and Smith because ‘680 is generic to a releasable linker and Smith specifically teaches a type of releasable linker that can couple a reagent on a support. The motivation to do so because cleavable linker system allows to eliminate redundant steps to allow for single step immunoassays to be performed in conjunction with a variety of detection agents and assay platforms (Smith par.12).
Claims 112 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-21, 27 and 38-40 of copending Application No. 17/200,680 (‘680) in view of Glezer (US20 200191779). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Application ‘680 teaches the method of claim 93 as discussed above but does not teach the limitations of claim 112.
Glezer teaches method for measuring the amount of analyte in a sample. See discussion in 93 above. Glezer teaches that a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent (see par.13); releasing said complex by cleaving said first binding reagent from said particle (see par.16), contacting said complex with a second binding reagent bound to a second solid phase, wherein said second binding reagent binds to said complex (see par.17), measuring the amount of said analyte bound to said second solid phase (see par.18).
The teaching of Glezer supports that the complex of capture reagent – analyte – detection reagent can be captured on a second solid support. By doing this, the analyte in the sample can be concentrated or purified so that it can improve the sensitivity of a subsequent measurement step or it can provide a uniform matrix for subsequent assay steps (see par.128).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of ‘680, releasing the capture reagent from the support, and capturing the complex of capture reagent – analyte – detection reagent on a second solid support in a method of detecting an analyte in a sample because Glezer teaches that the method can be used for purify or concentrating the analyte in a sample, which then significantly improve measurement accuracy and precision in binding assays, especially when analyzing complex biological samples (see Glezer par.101 and par.128). A person of ordinary skill in the art would have been motivated to combine ‘680 and Glezer to improve measurement accuracy and precision, especially when analyzing complex biological samples (see Glezer par(s).4, 101 and 128).
One having an ordinary skill in the art would have had a reasonable expectation of success in combine ‘680 and Glezer because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent.
Claims 93, 100-105 and 111-112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 29 and 31 of copending Application No. 17/711,731 (‘731) in view of Glezer (US20 200191779). Although the claims at issue are not identical, they are not patentably distinct from each other because:
For claim 93, claim 1 of 731 teaches a method of detecting and/or quantifying an analyte in a sample, the method comprising:(a) contacting the sample with a complex comprising: (i) a support, (ii) a capture reagent coupled to the support, (iii) a detection reagent releasably coupled to the support; (b) decoupling the detection reagent from the support; and (d) detecting one or both of the released detection reagent or capture reagent. ‘731 does not teach wherein the capture reagent and detection reagents are configured to simultaneously bind to the analyte, (c) decoupling the capture reagent from the support and the capture can be released from the support.
Glezer teaches method for measuring the amount of analyte bound to a solid phase (see par.11) comprising: contacting the sample with a complex comprising: a support and a capture reagent releasably coupled to the support and decoupling the capture reagent from the support (see par.6: teaching that contacting a sample comprising a target analyte with a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent; see par.23: teaching that releasing said complex by cleaving said first binding reagent from said particle).
Glezer also teaches the capture reagent and detection reagents are configured to simultaneously bind to the analyte (see at least par.24: teaching that contacting said complex with a second binding reagent, wherein said second binding reagent binds to said complex); and detecting one or both of the released detection reagent and capture reagent (see par(s).24-26: teaching that the complex of a first binding reagent, an analyte, a second binding reagent and detectable label is measured).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of ‘731, using a capture reagent releasably coupled to the support so that the capture reagent can be released from the support in a method of detecting an analyte in a sample because Glezer teaches that the method allows to concentrate an analyte in a sample and/or purify analytes in a sample for subsequent assay steps (see Glezer par.128). A person of ordinary skill in the art would have been motivated to combine ‘731 and Glezer to improve measurement accuracy and precision, especially when analyzing complex biological samples (see Glezer par.128: through concentration, it is often possible to significantly improve the sensitivity of a subsequent measurement step).
One having an ordinary skill in the art would have had a reasonable expectation of success in combine ‘731 and Glezer because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent.
For claims 100-101, 105 and 111, claim 1 of ‘731 teaches decoupling comprises applying a stimulus or decoupling comprises providing a displacer agent or a detectable displacer agent that decouples the detection reagent or the capture reagent from the support (step b, adding a detectably- labeled displacement agent which is also a biological stimulus). Claim 1 of ‘731 teaches the limitation of the instant claim 111.
For claims 102 and 104, claim 1 of ‘731 teaches detecting comprises identifying a nucleic acid molecule corresponding to the detection reagent or capture reagent (a detection barcode sequence is linked to a detection agent). According to the specification of ‘731, paragraph 210, a barcode sequence is a nucleic acid.
For claim 103, claims 29 and 31 of ‘731 teaches identifying the barcode is performed by a PCR reaction.
For claim 112, application ‘680 teaches the method of claim 93 as discussed above but does not teach the limitations of claim 112.
Glezer teaches method for measuring the amount of analyte in a sample. See discussion in 93 above. Glezer teaches that a particle linked to a first binding reagent that binds said target analyte and thereby forms a complex comprising said target analyte bound to said first binding reagent (see par.13); releasing said complex by cleaving said first binding reagent from said particle (see par.16), contacting said complex with a second binding reagent bound to a second solid phase, wherein said second binding reagent binds to said complex (see par.17), measuring the amount of said analyte bound to said second solid phase (see par.18).
The teaching of Glezer supports that the complex of capture reagent – analyte – detection reagent can be captured on a second solid support. By doing this, the analyte in the sample can be concentrated or purified so that it can improve the sensitivity of a subsequent measurement step or it can provide a uniform matrix for subsequent assay steps (see par.128).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of ‘731, releasing the capture reagent from the support, and capturing the complex of capture reagent – analyte – detection reagent on a second solid support in a method of detecting an analyte in a sample because Glezer teaches that the method can be used for purify or concentrating the analyte in a sample, which then significantly improve measurement accuracy and precision in binding assays, especially when analyzing complex biological samples (see Glezer par.101 and par.128). A person of ordinary skill in the art would have been motivated to combine ‘731 and Glezer to improve measurement accuracy and precision, especially when analyzing complex biological samples (see Glezer par(s).4, 101 and 128).
One having an ordinary skill in the art would have had a reasonable expectation of success in combine ‘731 and Glezer because they are directed to the method of detecting an analyte in a sample based on the detection of the complex of capture reagent - analyte - detection reagent.
Claims 94-99 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 29 and 31 of copending Application No. 17/711,731 (‘731) in view of Glezer (US20 200191779) and Smith (US20160153973). Although the claims at issue are not identical, they are not patentably distinct from each other because:
For claims 94-99, application ‘731 teaches the method of claim 93 as discussed above but does not teach the limitations of claims 94-99.
Smith teaches: the support further comprises a first anchor element and second anchor element coupled thereto (see Smith par.26 and Fig.1: teaching that both capture and detection antibodies are linked to the support via linkers 120 and 130), and the detection reagent is releasably coupled to the support via the second anchor element (see Smith in par(s).26-27: teaching that the linkers are linked to the support and the cleavable linker 130 is linked to the detection reagent);
the capture reagent comprises a first hook element coupled thereto, and wherein the first hook element is coupled to the first anchor element as in claims 95 and 97-99; the detection reagent comprises a second hook element coupled thereto, and wherein the second hook element is releasably coupled to the second anchor element as in claims 96 and 97-99; the support further comprises an anchor element coupled thereto, and wherein the capture reagent is releasably